The pyrimidine compound with which the present invention is concerned has the following structural formula ##STR1## and is known as buspirone. The hydrochloride salt has been referred to in the prior art as MJ 9022-1 and as buspirone hydrochloride. Other acid addition salts thereof are named by combining "buspirone" with the appropriate word to define the acid from which it is prepared as in "buspirone hydrochloride". The latter is the United States Adopted Name (USAN); refer to J. American Med. Assoc. 225. 520 (1973).
The synthesis of the compound and the disclosure of its psychotropic properties are described in the following patents and publications.
1. Y. H. Wu, et al., J. Med. Chem., 15.477 (1972). PA0 2. Y. H. Wu, et al., U.S. Pat. No. 3,717,634 which issued Feb. 20, 1973. PA0 3. L. E. Allen et al., Arzneium. Forsch., 24, No. 6, 917-922 (1974). PA0 4. G. L. Sathananthan, et al., Current Therapeutic Research. 18/5. 701-705 (1975). PA0 5. Y. H. Wu, et al., U.S. Pat. No. 3,976,776, issued Aug. 24. 1976. PA0 6. The use of buspirone hydrochloride as a novel antianxiety agent for the treatment of neurotic patients is described in G. P. Casten, et al., U.S. Pat. No. 4,182,763, issued Jan. 9, 1980. PA0 7. Allen, et al., disclose the use of buspirone in treating extrapyramidal motor disorders in U.S. Pat. No. 4,438,119issued Mar. 20, 1984. PA0 8. Buspirone's use in sexual dysfunction was described by Othmer, et al., in U.S. Pat. No. 4,640,921issued Feb. 3, 1987. PA0 9. Kurtz, et al., in U.S. Pat. No. 4,634,703, issued Jan. 6, 1987 disclose buspirone's use in treating panic disorders.
The following patent references disclose and claim additional uses which relate to buspirone's pharmacological effects on the central nervous system.
None of the above-referenced uses would in any way suggest the use of the present invention, a method for controlling and alleviating alcohol (ethanol) abuse.
While the structurally dissimilar benzodiazepine anxiolytics were known to potentiate the effects of alcohol and to successfully serve as a substitute for alcohol in certain patients; buspirone, in contrast, does not interact with alcohol (cf: Mattila, et al., J. Clin. Psychiatry, 43:12 (Sec. 2), pp. 56-61 (1982) and Seppala, et al., Clin. Pharmacol. Ther., 32:2, pp 201-207 (1982). In addition, buspirone does not elicit the euphoric mood typical of other known anxiolytic drugs in clinical use such as the benzodiazepines. Besides lacking physical dependence, buspirone also has no clinically demonstrable abuse potential. (cf: Cole, et al., J. Clin. Psychiatry 43:12 (Sec 2): pp 69-74 (1982): Griffith, et al., Am. J. Med. 80/3B: pp 30-35 (1986). In essence buspirone would not be merely a substitute for alcohol. Meyer in Journal of Studies on Alcohol, 47/4, 269-273 (1986) suggests that buspirone be studied for treating persistent anxiety in the postwithdrawal management of alcoholics on the basis that buspirone has a low potential for abuse and does not potentiate the effects of alcohol.
It is appreciated by one skilled in the art that prior art treatments designed to control alcohol abuse employ either "aversion therapy", e.g. disulfiram treatment (cf:AMA Drug Evaulations: 4th Edn. Chap. 14 "Drugs Used in Nonpsychotic Mental Disorders" pp. 209-214 (1980) Amer. Med. Soc., Chicago, Ill.) or "substitution", e.g. use of benzodiazepine anxiolytics. Clinical outcome of these treatments are controversial and do not represent effective treatment for the majority of patients that are chronic alcohol abusers.
Disulfiram (Antabuse.RTM.) is the only approved drug treatment for chronic alcohol abuse in the U.S. today. It causes a highly unpleasant reaction to alcohol ingestion but provides no other benefit to the chronic abuser of alcohol. Benzodiazepine anxiolytics are used in acute alcohol withdrawal treatment. However, these agents are not useful for definitive treatment of alcohol abuse since they substitute quite nicely for alcohol and can lead to a new dependence. It should be understood that no drug which actually treats the disorder of alcohol abuse per se is available. There is in fact, no really satisfactory drug treatment for abuse of alcohol at the present time.
It should also be appreciated that abuse of alcohol is a disorder affecting a large number of people and exacts a high cost in both physical and mental anguish. It has been estimated by The National Institute on Alcohol Abuse and Alcoholism that there are as many as 10 million alcoholics and problem drinkers in the U.S. alone. World estimates are several times as many.
There have been reports of agents that reduce alcohol intake in both animal and human studies.
The drug fluoxetine has been reported to reduce alcohol intake in rats, cf: Blinkerd, et al., Pharmacologist, 27/3, 283 (1985). ##STR2##
The drug zimelidine has been reported to reduce ethanol intake in rats and in non-depressed alcohol abusers. cf: Narangjo, et al., Clin. Pharmacol. and Therapeutic, 39/2, 215 (1986). ##STR3## As can be seen, there is no structural similarity between buspirone and fluoxetine, zimelidine, and the benzodiazepine class of compounds.
In summary, there exists nothing in the prior art, including the specific references set forth hereinabove, which would make obvious the use of buspirone to treat the abuse of alcohol.